These studies will attempt to further define the mechanisms regulating specific mammalian gene expression using erythropoiesis as a model system. Characterization of erythroid cell morphologically, genetically and biochemically provides a firm basis for further analyses of these cells. The control of globin and hemoglobin biosynthesis will be investigated at the levels of gene transcription, globin mRNA processing, globin translation and globin chain stabilization using human mutants with the thalassemia syndromes and related disorders, and mouse erythroid cells. Gene deletion, the presence of abnormal mRNAs and either decreased transcription or abnormal processing of globin mRNA, have already been identified as mechanisms for decreased alpha or beta globin synthesis in thalassemia. The availability of specific alpha or beta globin complementary DNAs (cDNAs) provide powerful tools for studying changes in DNA and mRNA processing in normal and abnormal erythroid cells. The specificity of globin chain specific cDNAs should permit analysis of the structure and organization of human globin genes in these cells. The mouse erythroleukemia cells (MELC) and mouse fetal liver cells also have unique advantages for study. MELC can be grown in continous culture and differentiate in response to variety of specific inducing agents, while early erythroid precursor cells can be isolated from mouse fetal liver cells and can be studied during their differentiaion in cell culture. Studies of erythropoiesis in mouse and man may lead to new insights into the processes controlling specific gene expression in mammalian cells and may provide new approaches to diagnosis, prevention and possible therapy of inherited anemias of man.